中文摘要：研究合成了一种肽载体Cys-Trp-Trp-Arg(8)-Cys-Arg(8)-Cys-Arg(8)-Cys，该载体整合了氧化还原反应二硫键交联和细胞穿透肽精氨酸八聚物，可用作疫苗传递载体。研究结果表明：肽载体通过显著增加IgG滴度、脾细胞增殖，促进INF-、IF12、IL-4和IL-10细胞因子分泌，增强免疫记忆功能和促进树突状细胞成熟等过程介导抗原特异性免疫反应；该结果提示，低分子量的疫苗-固定化学组成肽的冷凝组合物能够形成一种新型疫苗传递系统。
外文摘要：In immunotherapy, induction of potent cellular immunity by vaccination is essential to treat intracellular infectious diseases and tumors. In this work, we designed a new synthetic peptide carrier, Cys-Trp-Trp-Arg(8)-Cys-Arg(8)-Cys-Arg(8)-Cys, for vaccine delivery by integrating a redox-responsive disulfide bond cross-linking and cell-penetrating peptide arginine octamer. The carrier peptide bound to the antigen protein ovalbumin (OVA) via electrostatic self-assembly to form peptide/OVA nanocomposites. Then, the spontaneous oxidization of the thiols of the cysteine residues induced interpeptide disulfide bond cross-linking to construct denser peptide/OVA condensates. The cell-penetrating peptides incorporated in the carrier peptide could increase antigen uptake by antigen presenting cells. After being internalized by antigen presenting cells, the antigen could be rapidly released in cytoplasm along with degradation of the disulfide bonds by intracellular glutathione, which could promote potent CD8(+) T cell immunity. The cross-linked peptide/OVA condensates were used for subcutaneous vaccination. The results showed that the peptide carrier mediated potent antigen-specific immune response by significantly increasing IgG titer; splenocyte proliferation; the secretion level of cytokines INF-gamma, IL-12, IL-4, and IL-10; immune memory function, and the activation and maturation of dendritic cells. From the results, the low-molecular weight vaccine-condensing peptide with definite chemical composition could be developed as a novel class of vaccine delivery systems.
外文关键词：vaccine delivery system, redox-responsive, cell-penetrating peptides, cellular immunity
作者：Wang, KW; Yang, Y; Xue, W; Liu, ZH
作者单位：广东暨南大学
期刊名称：MOLECULAR PHARMACEUTICS
期刊影响因子：4.44
出版年份：2018
出版刊次：3
点击下载：一种皮下接种氧化还原敏感疫苗的传递系统——细胞穿透肽
